Nevirapine-D4

117.5 kg of 2-chloro-N-(2-chloro-4-methyl-3-pyridyl)-3-pyridine carboxamide (4), 46.7 kg of calcium oxide and 47.5 kg of cyclopropylamine (molar ratio: 1:2:2) are heated to 135° to 145° C. in 235 l of diglyme (diethylene glycol dimethylether) in a 500 l VA autoclave over a period of 6 to 8 hours. The reaction mixture is then cooled to a temperature of 20° to 30° C. and filtered. The filter cake is washed with 58.8 l of diglyme. The filtrates are combined and about 188 l of solvent is distilled off. The residue is then diluted with a further 117.5 l of diglyme. Over a period of 20 to 40 minutes, the resultant diluted solution is added to a suspension of 45.0 kg of 60% sodium hydride in 352.5 l of diglyme, heated to 130° C. The storage vessel and conduits are rinsed with a further 55.8 l of diglyme and the mixture is stirred at a temperature of 130° to 140° C. for a further 30 to 60 minutes. The majority of the diglyme is then distilled off. Finally, the remaining residue is carefully mixed with 470.0 l of water. The reaction mixture is cooled to a temperature of about 25° C. and 235.0 l of cyclohexane and 57.1 l of glacial acetic acid are added. The mixture is then stirred for about 1 hour at a temperature of 10° to 25° C. The resultant suspension is centrifuged and the centrifuged material is washed with 235.0 l of methyl tert.-butylether, followed by 353.5 l of water and finally with 235 l of ethanol. In this way, after drying, 90.6 kg (81.7% of theory) of 11-cyclopropyl-5,11-dihydro-4-methyl-6H-dipyrido-[3,2-b:2',3'-e][1,4]diazepin-6-one (nevirapine) is isolated.

117.5 kg of 2-chloro-N-(2-chloro-4-methyl-3-pyridyl)-3-pyridine carboxamide (4), 46.7 kg of calcium oxide and 47.5 kg of cyclopropylamine (molar ratio: 1:2:2) are heated to 135° to 145° C. in 235 l of diglyme (diethylene glycol dimethylether) in a 500 l VA autoclave over a period of 6 to 8 hours. The reaction mixture is then cooled to a temperature of 20° to 30° C. and filtered. The filter cake is washed with 58.8 l of diglyme. The filtrates are combined and about 188 l of solvent is distilled off. The residue is then diluted with a further 117.5 l of diglyme. Over a period of 20 to 40 minutes, the resultant diluted solution is added to a suspension of 45.0 kg of 60% sodium hydride in 352.5 l of diglyme, heated to 130° C. The storage vessel and conduits are rinsed with a further 55.8 l of diglyme and the mixture is stirred at a temperature of 130° to 140° C. for a further 30 to 60 minutes. The majority of the diglyme is then distilled off. Finally, the remaining residue is carefully mixed with 470.0 l of water. The reaction mixture is cooled to a temperature of about 25° C. and 235.0 l of cyclohexane and 57.1 l of glacial acetic acid are added. The mixture is then stirred for about 1 hour at a temperature of 10° to 25° C. The resultant suspension is centrifuged and the centrifuged material is washed with 235.0 l of methyl tert.-butylether, followed by 353.5 l of water and finally with 235 l of ethanol. In this way, after drying, 90.6 kg (81.7% of theory) of 11-cyclopropyl-5,11-dihydro-4-methyl-6H-dipyrido-[3,2-b:2',3'-e][1,4]diazepin-6-one (nevirapine) is isolated.